Association between selenium species and hippocampal volume in subjects with mild cognitive impairment

BACKGROUND AND AIM. Selenium is a trace element with nutritional and toxicological properties. Its influence on human health is thought to depend on exposure dose and chemical form. The effects of selenium exposure on medical conditions that involve the central nervous system have been understudied. In a cohort of individuals with mild cognitive impairment, we have previously documented a positive relation between cerebrospinal fluid (CSF) levels of inorganic hexavalent selenium (selenate) and risk of dementia. METHODS. We assessed the relation between CSF levels of selenium species and volume of the hippocampus among the 33 cohort members aged 43-82 years who had undergone magnetic resonance imaging at baseline (2008-2014) using both linear and spline regression analyses. We also performed a surface-based analysis using SPHARM-PDM to evaluate differences in shape of the hippocampus in addition to its volume in relation to CSF levels of selenium species. RESULTS. We found an inverse association between selenate and total hippocampal volume (β regression coefficient in multivariable linear regression analysis -3.05, 95% confidence interval -5.74 to -0.37), which was similar for the right and left hippocampus and emerged mainly at the highest exposure levels. We found little association between the other selenium forms and hippocampal volume. In the surface-based analysis, the left hippocampus showed considerably more pronounced shape differences in the ventro-medial region of the head. CONCLUSIONS. This is the first study to analyze selenium species in relation to hippocampal volume and structure, suggesting that a selenium form with high toxicological potential may adversely affect a key structure involved in dementia onset and progression as the hippocampus, possibly the left one in particular. However, we cannot entirely rule out the influence of reverse causation or unmeasured confounding on these results. Keywords: Mild cognitive impairment; Dementia; Alzheimer’s dementia; Hippocampus; Magnetic resonance imaging; Cerebrospinal fluid; Selenium; selenate